Regenerative agriculture (RA) is gaining traction globally as an approach for meeting growing food demands while avoiding, or even remediating, the detrimental environmental consequences associated with conventional farming. Momentum is building for science to provide evidence for, or against, the putative ecosystem benefits of RA practices relative to conventional farming. In this perspective article, we advance the argument that consideration of the soil microbiome in RA research is crucial for disentangling the varied and complex relationships RA practices have with the biotic and abiotic environment, outline the expected changes in soil microbiomes under RA, and make recommendations for designing research that will answer the outstanding questions on the soil microbiome under RA. Ultimately, deeper insights into the role of microbial communities in RA soils will allow the development of biologically relevant monitoring tools which will support land managers in addressing the key environmental issues associated with agriculture.